Use of Advanced Diagnostics for Timely Identification of Travel-associated Leptospira santarosai Infection in Four Adolescents Through Plasma Microbial Cell-free DNA Sequencing With the Karius Test.

BACKGROUND: Leptospirosis is an important zoonotic infection worldwide. Diagnosis of leptospirosis is challenging given its nonspecific clinical symptoms that overlap with other acute febrile illnesses and limitations with conventional diagnostic testing. Alternative advanced diagnostics, such as microbial cell-free DNA (mcfDNA), are increasingly being used to aid in the diagnosis of infections and can be applied to pathogens with public health importance such as Leptospira , a nationally notifiable disease. METHODS: The Karius Test uses plasma mcfDNA sequencing to detect and quantify DNA-based pathogens. This test offered through the Karius lab detected 4 cases of Leptospira santarosai during a 5-month period across the United States in 2021 and were clinically reviewed. RESULTS: In our case series, 4 adolescents with recent travel to Central America (Costa Rica, n = 3 and Belize, n = 1) from April to August 2021 were diagnosed with leptospirosis. While a large workup was performed in all cases, mcfDNA testing was the first test to detect L. santarosai as the microbiological diagnosis in all cases. CONCLUSIONS: Results of the Karius Test enabled rapid, noninvasive diagnosis of leptospirosis allowing for targeted therapy. Use of mcfDNA can be utilized for diagnosis of pathogens where conventional testing is challenging or limited. This in turn can enable quick diagnosis for targeted treatment and potentially aid in supporting case definitions of reportable diseases of public health concern.

Impact of a school-based influenza immunization program on disease burden: comparison of two Tennessee counties.

Outpatient burden of laboratory-confirmed influenza among children in Knox and Davidson Counties was compared in 2006-2007 when only Knox County had a school-based influenza vaccine campaign. Of 1016 eligible children seeking outpatient care, 87% were enrolled and 20% were influenza-positive. Estimated influenza vaccination coverage was similar in Knox and Davidson for preschool-age children (36% versus 33%) but higher in Knox County for school-age children (44% versus 12%). Influenza detection was higher among Knox than Davidson County preschool-age children (18% versus 10%) but similar among school-age children (28% versus 27%). These data are consistent with a direct effect of the campaign in school-age children.

Human monocytic ehrlichiosis in children.

BACKGROUND: Human monocytic ehrlichiosis (HME) is a tick-borne illness caused by Ehrlichia chaffeensis. Data about disease in children have been largely derived from case reports or small case series. METHODS: A retrospective review of all medical and laboratory records from 6 sites located in the "tick belt" of the Southeastern United States was carried out. Demographic, history and laboratory data were abstracted from the identified medical records of patients. Bivariate statistical comparisons were performed using Fisher exact test or Wilcoxon rank sum tests. RESULTS: Common clinical signs and symptoms of patients with HME (n = 32) included fever (100%), headache (69%), myalgia (69%), rash (66%), nausea/vomiting (56%), altered mental status (50%) and lymphadenopathy (47%). Only 48% had a complaint of fever, headache and rash. Common laboratory abnormalities included thrombocytopenia (94%), elevated aspartate aminotransferase (90%), elevated alanine aminotransferase (74%), hypoalbuminemia (65%), lymphopenia (57%), leukopenia (56%) and hyponatremia (55%). The median number of days of illness before the initiation of antirickettsial therapy was 6. Patients who received sulfonamides before starting doxycycline therapy developed a rash, were admitted to the hospital, and started doxycycline at a later date. Twenty-two percent of patients were admitted to the intensive care unit with 12.5% of patients requiring ventilatory and blood pressure support. CONCLUSIONS: Although HME has been recognized among children for almost 20 years, there is only a limited knowledge about its clinical course. Even among physicians practicing in endemic regions, few cases are diagnosed each year. More work is needed to understand the true burden of disease and the natural history among asymptomatically and symptomatically infected children.

Clinical and laboratory features, hospital course, and outcome of Rocky Mountain spotted fever in children.

OBJECTIVES: To describe the clinical characteristics and course of children with laboratory-diagnosed Rocky Mountain spotted fever (RMSF) and to identify clinical findings independently associated with adverse outcomes of death or discharge with neurologic deficits. STUDY DESIGN: Retrospective chart review of 92 patients at six institutions in the southeastern and southcentral United States from 1990 to 2002. Statistical analyses used descriptive statistics and multiple logistic regression. RESULTS: Children with RMSF presented to study institutions after a median of 6 days of symptoms, which most commonly included fever (98%), rash (97%), nausea and/or vomiting (73%), and headache (61%); no other symptom or sign was present in >50% of children. Only 49% reported antecedent tick bites. Platelet counts were <150,000/mm3 in 59% of children, and serum sodium concentrations were <135 mEq/dL in 52%. Although 86% sought medical care before admission, only 4 patients received anti-rickettsial therapy during this time. Three patients died, and 13 survivors had neurologic deficits at discharge. Coma and need for inotropic support and intravenous fluid boluses were independently associated with adverse outcomes. CONCLUSIONS: Children with RMSF generally present with fever and rash. Delays in diagnosis and initiation of appropriate therapy are unacceptably common. Prognosis is guarded in those with hemodynamic instability or neurologic compromise at initiation of therapy.

Clinical comparisons of La Crosse encephalitis and enteroviral central nervous system infections in a pediatric population: 2001 surveillance in East Tennessee.

BACKGROUND: La Crosse encephalitis (LAC) is a mosquito-borne illness that primarily affects children. In 1997, an initial cluster of cases was identified by the regional pediatric referral center in East Tennessee. Since that time, public health officials, pediatric infectious disease physicians, infection control nurses, laboratory personnel, entomologists, and Centers for Disease Control and Prevention consultants have collaborated to provide ongoing surveillance activities. Studies comparing LAC cases with non-LAC (no etiologic diagnosis) central nervous system infections have yielded no statistical significance in signs and symptoms or laboratory values. OBJECTIVE: To determine any differences in signs, symptoms, and/or diagnostic laboratory values between LAC cases and enteroviral central nervous system (EV-CNS) infections. METHODS: In 2001, descriptive public health surveillance for LAC was performed concurrent with an outbreak investigation of EV-CNS infections at a pediatric referral center in East Tennessee. All patients being evaluated for suspected meningitis and/or encephalitis were interviewed for signs and symptoms of illness. Patients with positive test results for LAC and negative results for EV or positive results for EV and negative results for LAC were included in the study. RESULTS: Compared with patients with EV-CNS infection, patients with LAC were significantly more likely to have aphasia (P=.001), loss of consciousness (P=.0003), seizure (P=.0003), and admission to the pediatric intensive care unit (P=.02). Presence of fever, headache, vomiting, stiff neck (subjective), photophobia, behavioral changes, confusion, need for mechanical ventilation, age, and sex showed no statistical significance (P>.05). Statistical differences were not demonstrated in cerebrospinal fluid laboratory values (P>.05). CONCLUSION: Patients with LAC demonstrated more severe symptoms on presentation to the hospital than did patients with EV-CNS infection. A possible advantage of identifying specific viral etiologic factors of pediatric CNS disease by clinical characteristics may be the ability to take advantage of emerging antiviral therapies.

Linezolid for the treatment of complicated skin and skin structure infections in children.

BACKGROUND: Gram-positive pathogens are a major cause of complicated skin and skin structure infections (CSSSIs) in children. Many pathogens are developing decreased susceptibility to currently used antibiotics, increasing the need for new therapies. Linezolid is well-tolerated and effective in the treatment of these infections in adults. OBJECTIVE: To evaluate the clinical efficacy and safety of iv/oral linezolid and iv vancomycin in children with Gram-positive CSSSIs. METHODS: Hospitalized children <12 years of age were randomized (2:1 ratio) to receive either linezolid 10 mg/kg iv every 8 h (with the option to change treatment to oral linezolid suspension 10 mg/kg every 8 h) or iv vancomycin 10 to 15 mg/kg every 6 to 24 h (according to age). Clinical response, tolerance and safety were evaluated at follow-up. The results of a subset analysis of patients with CSSSIs are presented here. RESULTS: One hundred twenty intent-to-treat patients (linezolid 80, vancomycin 40) with CSSSI were included in this analysis. Clinical cure rates for clinically evaluable patients with CSSSI did not differ between treatment groups (linezolid, 93.2% vs. vancomycin, 90.0%; P = 0.594). Significantly fewer linezolid-treated patients experienced drug-related adverse events than did vancomycin-treated patients (23% vs. 48%; P = 0.006). The percentages of patients with laboratory abnormalities, including selected hematologic parameters, were generally low and similar between the treatment groups. CONCLUSIONS: Linezolid given iv or orally was well-tolerated and safe. It was as effective as vancomycin in treating children with Gram-positive CSSSIs.

La Crosse encephalitis in Eastern Tennessee: clinical, environmental, and entomological characteristics from a blinded cohort study.

A blinded cohort study was conducted in 2000 to better understand the emergence of La Crosse virus infection in eastern Tennessee, with special emphasis on the potential mosquito vector(s). Children with suspected central nervous system infection were enrolled at the time of clinical presentation at a large pediatric referral hospital. Clinical, environmental, and entomological data were collected prior to case confirmation. Sixteen of the 40 children included in the final analysis were confirmed to have La Crosse infection by a fourfold increase in antibody titers between collection of acute- and convalescent-phase sera. Factors significantly associated with La Crosse infection included average number of hours per day spent outdoors (5.9 for La Crosse virus cases vs. 4.0 for noncases, p = 0.049); living in a residence with one or more tree holes within 100 m (relative risk = 3.96 vs. no tree holes within 100 m, p = 0.028); and total burden of Aedes albopictus (number of female and male larvae and adults collected at a site), which was more than three times greater around the residences of La Crosse virus cases versus noncases (p = 0.013). Evidence is accumulating that the newly introduced mosquito species Ae. albopictus may be involved in the emergence of La Crosse virus infection in eastern Tennessee.